CA3165468A1 - Combinations - Google Patents
CombinationsInfo
- Publication number
- CA3165468A1 CA3165468A1 CA3165468A CA3165468A CA3165468A1 CA 3165468 A1 CA3165468 A1 CA 3165468A1 CA 3165468 A CA3165468 A CA 3165468A CA 3165468 A CA3165468 A CA 3165468A CA 3165468 A1 CA3165468 A1 CA 3165468A1
- Authority
- CA
- Canada
- Prior art keywords
- unsubstituted
- substituted
- cancer
- alkyl
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 150000003839 salts Chemical class 0.000 claims abstract description 91
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
- 201000010099 disease Diseases 0.000 claims abstract description 37
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 29
- 239000003112 inhibitor Substances 0.000 claims abstract description 24
- 101000621390 Homo sapiens Wee1-like protein kinase Proteins 0.000 claims abstract description 21
- 102100023037 Wee1-like protein kinase Human genes 0.000 claims abstract description 21
- 201000011510 cancer Diseases 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 109
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- -1 hydroxy, amino Chemical group 0.000 claims description 47
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 46
- 125000004429 atom Chemical group 0.000 claims description 37
- 125000003277 amino group Chemical class 0.000 claims description 25
- 125000002947 alkylene group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 125000001188 haloalkyl group Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 150000003973 alkyl amines Chemical class 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
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- BKWJAKQVGHWELA-UHFFFAOYSA-N 1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methyl-1-piperazinyl)anilino]-2-prop-2-enyl-3-pyrazolo[3,4-d]pyrimidinone Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)N(CC=C)N(C=3N=C(C=CC=3)C(C)(C)O)C2=N1 BKWJAKQVGHWELA-UHFFFAOYSA-N 0.000 claims description 3
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- 206010057644 Testis cancer Diseases 0.000 claims description 3
- 229950009557 adavosertib Drugs 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
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- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 2
- 206010061424 Anal cancer Diseases 0.000 claims description 2
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 2
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- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 2
- 206010034299 Penile cancer Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims description 2
- 206010046392 Ureteric cancer Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 201000011165 anus cancer Diseases 0.000 claims description 2
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 201000010175 gallbladder cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
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- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 2
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- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000020984 malignant renal pelvis neoplasm Diseases 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 206010038038 rectal cancer Diseases 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 201000007444 renal pelvis carcinoma Diseases 0.000 claims description 2
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- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 201000011294 ureter cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 210000004291 uterus Anatomy 0.000 claims description 2
- 239000012664 BCL-2-inhibitor Substances 0.000 abstract 1
- 229940123711 Bcl2 inhibitor Drugs 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 description 49
- 125000004432 carbon atom Chemical group C* 0.000 description 42
- 125000001072 heteroaryl group Chemical group 0.000 description 42
- 125000002950 monocyclic group Chemical group 0.000 description 38
- 125000005842 heteroatom Chemical group 0.000 description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
- 125000002619 bicyclic group Chemical group 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 description 18
- 125000003342 alkenyl group Chemical group 0.000 description 17
- 125000000304 alkynyl group Chemical group 0.000 description 17
- 239000008194 pharmaceutical composition Substances 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 150000002431 hydrogen Chemical class 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 229940125904 compound 1 Drugs 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 125000003003 spiro group Chemical group 0.000 description 9
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
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- 239000002904 solvent Substances 0.000 description 5
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- 208000024891 symptom Diseases 0.000 description 5
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 101001132698 Homo sapiens Retinoic acid receptor beta Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 4
- 102100033909 Retinoic acid receptor beta Human genes 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
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- PSNDWZOXFDKLLH-UHFFFAOYSA-N 2-azaspiro[3.4]octane Chemical compound C1NCC11CCCC1 PSNDWZOXFDKLLH-UHFFFAOYSA-N 0.000 description 3
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- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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Landscapes
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Glass Compositions (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Steroid Compounds (AREA)
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| US201962952059P | 2019-12-20 | 2019-12-20 | |
| US62/952,059 | 2019-12-20 | ||
| PCT/US2020/065406 WO2021127041A1 (en) | 2019-12-20 | 2020-12-16 | Combinations |
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| CA3165468A1 true CA3165468A1 (en) | 2021-06-24 |
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| EP2155752B1 (en) * | 2007-04-25 | 2018-09-19 | Merck Sharp & Dohme Corp. | Polymorph of dihydropyrazolopyrimidinone derivative as weel kinase.inhibitor |
| PT2477628E (pt) * | 2009-09-15 | 2014-11-25 | Merck Sharp & Dohme | Preparação de formas de hemihidrato cristalino de dihidropirazolopirimidinona |
| MX369518B (es) * | 2012-08-16 | 2019-11-11 | Novartis Ag | Combinacion de inhibidor de p13k e inhibidor de c-met. |
| PL2925888T3 (pl) * | 2012-11-28 | 2018-03-30 | Merck Sharp & Dohme Corp. | Kompozycje i sposoby do stosowania w leczeniu nowotworów |
| US11613545B2 (en) * | 2017-11-01 | 2023-03-28 | Wuxi Biocity Biopharmaceutics Co., Ltd. | Macrocyclic compound serving as Wee1 inhibitor and applications thereof |
| AU2019207608B2 (en) * | 2018-01-10 | 2024-03-28 | Recurium Ip Holdings, Llc | Benzamide compounds |
| WO2019169065A2 (en) * | 2018-02-28 | 2019-09-06 | The Regents Of The University Of Colorado, A Body Corporate | Wee1 kinase inhibitors and methods of treating cancer using the same |
-
2020
- 2020-12-16 JP JP2022538226A patent/JP2023508331A/ja active Pending
- 2020-12-16 CN CN202080095196.0A patent/CN115023229A/zh active Pending
- 2020-12-16 EP EP20901758.1A patent/EP4069234A4/en active Pending
- 2020-12-16 WO PCT/US2020/065406 patent/WO2021127041A1/en unknown
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- 2020-12-16 BR BR112022012284A patent/BR112022012284A2/pt unknown
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- 2020-12-16 US US17/757,490 patent/US20230065577A1/en active Pending
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| KR20220119427A (ko) | 2022-08-29 |
| AU2020404995A1 (en) | 2022-07-14 |
| EP4069234A4 (en) | 2024-01-03 |
| MX2022007625A (es) | 2022-08-16 |
| WO2021127041A1 (en) | 2021-06-24 |
| JP2023508331A (ja) | 2023-03-02 |
| BR112022012284A2 (pt) | 2022-08-30 |
| IL294081A (en) | 2022-08-01 |
| US20230065577A1 (en) | 2023-03-02 |
| EP4069234A1 (en) | 2022-10-12 |
| TW202135814A (zh) | 2021-10-01 |
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